These studies are addressed to the question of the nature of cellular events in adipose tissue and in liver that accompany or precede obesity as it is manifest in the genetically obese Zucker rat (fafa). We are analyzing events at the tissue, cellular and subcellular levels that characterize the proliferation and differentiation of adipose tissue and are monitoring metabolic changes in fetal and neonatal hepatocytes that may precede or coincide with an increased lipogenic capacity in the obese Zucker rat. Our goal is to identify the way in which the fatty (fa) gene is acting to produce a lesion which ultimately leads to the development of hyperplastic obesity with its coincident metabolic defects; e.g., hyperinsulinemia and hyperlipidemia. We believe that unravelling the developmental sequence of events leading to obesity in the Zucker rat may aid our understanding of the etiology of hyperplastic obesity of early-onset in the human.